Synthetic somatostatin analog (octreotide) suppresses daytime growth hormone secretion equivalently in young and older men: Preserved pituitary responsiveness to somatostatin's inhibition in aging

OBJECTIVE: To gain greater insight into the mechanisms controlling the low daytime rate of growth hormone (GH) secretion in older men. DESIGN: We conducted a randomized, controlled study of GH secretion during inhibition by octreotide, a somatostatin analog. PARTICIPANTS: Nine young (35-44 years) and ten older (62-79 years) healthy men participated. INTERVENTION: Octreotide versus nothing, while subjects were on a standardized diet. MEASUREMENTS: All subjects were assessed on two separate occasions: baseline and at time of the intervention of octreotide (100 μg subcutaneously); the order of the intervention was randomly assigned. Octreotide was administered at 8:00 a.m. Venous sampling was performed every 10 minutes for 8 hours (8:30 a.m. to 4:30 p.m.). To estimate the joint parameters of pulsatile and basal (between secretory pulses) GH secretion, we used an ultrasensitive chemiluminescence- based GH assay and multiparameter deconvolution analysis. RESULTS: Compared with baseline, octreotide markedly reduced mean (8-hour) serum GH concentrations in both young (0.585 ± 0.255 μg/L vs 0.070 ± 0.029 μg/L;P = .008) and older (0.397 ± 0.107 μg/L vs 0.087 ± 0.027 μg/L;P = 0.005) men. In younger men, octreotide decreased the serum GH concentration primarily by suppressing the mass of GH released per secretory pulse (2.4 ± 0.9 μg/L vs 1.0 ± .7 μg/L;P = .015) and the interpulse (basal) rate of GH release (0.0014 ± 0.0003 μg/L/min vs 0.0006 ± 0.0002 μg/L/min;P = .051). In older men, octreotide also restrained the mass of GH per secretory pulse (1.5 ± 0.4 μg/L vs 0.4 ± 0.1 μg/L; P = .028) and lowered basal GH release (0.0014 ± 0.0003 μg/L/min vs 0.0004 ± 0.0001 μg/L/min; P = .007). There were no significant differences when the older men were compared with the young controls. CONCLUSIONS: Our data suggest that the daytime relative GH deficiency seen in older men is not a result of excessive pituitary susceptibility to the inhibitory capabilities of somatostatin, but more likely reflects impoverished endogenous GHRH drive and/or heightened release of brain somatostatin.